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810 Part VI: The Erythrocyte Chapter 52: Erythrocyte Disorders as a Result of Chemical and Physical Agents 811

A B C
Figure 52–1. A. Blood film prepared at admission from a patient who had suffered severe burn injury involving a large percentage of the body
surface. Note the presence of normal erythrocytes (apparently from vessels not exposed to heat damage) along with populations of normocytic
and microcytic spherocytes. In addition, there are numerous red cell fragments, some smaller than platelets. B. Blood film prepared from a patient
exposed to arsenic hydride. Note the very pale red cells resulting from partial hemoglobin loss secondary to membrane damage. An extreme exam-
ple, represented by the virtual ghost thinly rimmed with scant residual hemoglobin, can be found in the upper left-hand corner. C. Wilson disease.
In this image from a patient with Wilson disease, there are numerous visible sequelae of oxidative damage caused by excess copper. The striking
microspherocytosis indicates damage to the membrane. Damage to hemoglobin is demonstrated by the Heinz bodies projecting from red cells
(asterisks show two examples). The horizontal arrow points to one of several spherocytes. The vertical arrow points to a macrocyte (reticulocyte). An
occasional cell shows damage to both membrane and hemoglobin. The presence of echinocytes (oblique arrows show two examples) suggests that
the liver is also affected. (A & B, reproduced with permission from Lichtman’s Atlas of Hematology, www.accessmedicine.com. C, used with permission of
Barbara J. Bain, Imperial College, London, UK.)

some countries for a variety of therapeutic purposes, had no apparent CHEMICAL AND PHYSICAL AGENTS
effect in vivo on red cell enzymes and intermediates at the 30 mcg/mL
concentration commonly infused, but did produce some in vitro hemo- NOT DEFINITIVELY DESCRIBED
lysis at that concentration. 37 MECHANISTICALLY
Arsenic Hydride A variety of chemical and physical agents cause erythrocyte disorders
Arsenic exposure is a major cause of anemia in regions with high envi- through unknown or not well-characterized mechanisms. There are
ronmental concentration. Examples include Bangladesh’s tainted water isolated reports of hemolytic anemia occurring after the administra-
supply, and areas of China where arsenic laden coal is used. Arsine gas tion of a variety of chemical substances, some of which are listed in
38
(arsenic hydride, AsH ) is the most erythrotoxic form of arsenic and Table 52–1. What follows is a collection of miscellaneous erythrocyte
3
inhalation of arsine gas is a well-recognized cause of hemolytic anemia damaging agents and processes for which the mechanisms are still
(see Fig. 52–1B). 39–41 Arsine is formed during many industrial processes, largely undefined or disputed.
including the reaction of hydrogen with available arsenic compounds in
metallurgic processes. The arsenic is usually a contaminant, so contact NEOCYTOLYSIS
with arsenic compounds may not be apparent from the patient’s history.
The mechanism of erythrocyte damage occurs via oxidation of sulfhydryl Astronauts experience significant anemia after space flight even in the
35
groups in the erythrocyte membrane and associated cytoskeleton, 42,43 presence of normal or elevated ambient oxygen concentration. The
and decreased levels of reduced glutathione in erythrocytes exposed to
AsH are observed. 44
3
TABLE 52–1. Drugs and Chemicals That Have Been
Chlorates and Chloramines Reported to Cause Hemolytic Anemia Secondary to
Sodium and potassium chlorate are oxidative drugs that produce methe- Erythrocyte Damage
moglobinemia, Heinz bodies, and hemolytic anemia. Although it has Chemicals Drugs
45
been presumed that the mechanism of hemolysis is similar to that resulting
from other oxidative drugs, enigmatically, no cases have been observed in Aniline 86 Amyl nitrite 94
patients deficient in glucose-6-phosphate dehydrogenase (G6PD). Hemo- Apiol 87 Mephenesin 95
lytic anemia with Heinz body formation has also occurred in patients Dichlorprop (herbicide) 88 Methylene blue 96
undergoing dialysis when the water contained a substantial amount of
chloramines. Oxidative damage to the red cells of these patients was Formaldehyde 48 Omeprazole 97
demonstrated by the presence of Heinz bodies, a positive ascorbate-cya- Hydroxylamines 89 Pentachlorophenol 98
nide test, and methemoglobinemia. 46,47
Lysol 90 Phenazopyridine (Pyridium) 99
Formaldehyde Mineral spirits 91 Salicylazosulfapyridine
Leaching of formaldehyde from plastic used in water filters employed (Azulfidine) 100
for hemodialysis is also a cause of hemolytic anemia. The low level of Nitrobenzene 92 Tacrolimus 101
formaldehyde in the contaminated water does not result in a fixative Resorcin 93
effect, but instead induces metabolic changes within the red cells. 48

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